The Oxidation of Lipoproteins by Monocytes-Macrophages

Chisolm, Guy M.; Hazen, Stanley L.; Fox, Paul L.; Cathcart, Martha K.

doi:10.1074/jbc.274.37.25959

Cited by 160 publications

(100 citation statements)

References 118 publications

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“…A number of large clinical trials have shown no decrease in cardiovascular disease after antioxidant supplementation, however, and the importance of oxidised LDL in atherosclerosis is therefore an unresolved issue [2]. Several studies have demonstrated that LDL can be oxidised in vitro by cells associated with atherosclerotic lesions [3][4][5][6][7]. The mechanisms of LDL oxidation in vivo are controversial [1].…”

Section: Introductionmentioning

confidence: 99%

Mechanism of the antioxidant to pro-oxidant switch in the behavior of dehydroascorbate during LDL oxidation by copper(II) ions

Horsley

Burkitt

Jones

et al. 2007

Archives of Biochemistry and Biophysics

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Subject area: Systems biochemistryAbbreviations: BCDS, bathocuproine disulphonic acid; DMPO,5, EPR, electron paramagnetic resonance; 13-HPODE, 13(S)-hydroperoxyoctadeca-9Z,11E-dienoic acid 2 ABSTRACTOxidised low density lipoprotein (LDL) may be involved in the pathogenesis of atherosclerosis.We have therefore investigated the mechanisms underlying the antioxidant/pro-oxidant behavior of dehydroascorbate, the oxidation product of ascorbic acid, toward LDL incubated with Cu 2+ ions. By monitoring lipid peroxidation through the formation of conjugated dienes and lipid hydroperoxides, we show that the pro-oxidant activity of dehydroascorbate is critically dependent on the presence of lipid hydroperoxides, which accumulate during the early stages of oxidation.Using electron paramagnetic resonance spectroscopy, we show that dehydroascorbate amplifies the generation of alkoxyl radicals during the interaction of copper ions with the model alkyl hydroperoxide, tert-butylhydroperoxide. Under continuous-flow conditions, a prominent doublet signal was detected, which we attribute to both the erythroascorbate and ascorbate free radicals.On this basis, we propose that the pro-oxidant activity of dehydroascorbate toward LDL is due to its known spontaneous interconversion to erythroascorbate and ascorbate, which reduce Cu 2+ to Cu + and thereby promote the decomposition of lipid hydroperoxides. Various mechanisms, including copper chelation and Cu + oxidation, are suggested to underlie the antioxidant behavior of dehydroascorbate in LDL that is essentially free of lipid hydroperoxides.

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Section: Introductionmentioning

confidence: 99%

Mechanism of the antioxidant to pro-oxidant switch in the behavior of dehydroascorbate during LDL oxidation by copper(II) ions

Horsley

Burkitt

Jones

et al. 2007

Archives of Biochemistry and Biophysics

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“…LDL oxidation is a progressive process resulting in the formation of mildly oxLDL (de®ned by low lipid peroxidation derivatives content and only minor apoB modi®cations), and leading ®nally to extensively oxLDL (characterized by high levels of lipid peroxidation derivatives and severe apoB alterations). LDL oxidation is promoted in vitro by a variety of oxidizing agents (Berliner & Heinecke, 1996;Chisolm et al, 1999) and is believed to be mediated in vivo by reactive oxygen species and free radicals generated by vascular cells (Witztum & Steinberg, 1991;Berliner & Heinecke, 1996).…”

Section: Introductionmentioning

confidence: 99%

Phenolic antioxidants trolox and caffeic acid modulate the oxidized LDL‐induced EGF‐receptor activation

Vacaresse

Vieira

Robbesyn

et al. 2001

British J Pharmacology

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1 Oxidized low density lipoproteins (oxLDL) are thought to play a major role in atherosclerosis. OxLDL act in part through alteration of intracellular signalling pathways in cells of the vascular wall. We recently reported that the EGF receptor (EGFR) signalling pathway is activated by lipid peroxidation products (among them 4-hydroxynonenal, 4-HNE) contained in oxLDL. 2 The use of phenolic antioxidants, such as trolox, alpha-tocopherol, ca eic acid and tyrphostins A-25, A-46 or A-1478, showed that the oxLDL-induced EGFR activation is constituted by two separate components, the ®rst (early) one being antioxidant-insensitive, the second (late) being antioxidant-sensitive. 3 4-HNE derivatization of EGFR and EGFR activation induced by exogenous 4-HNE, suggest that the early (0.5 ± 3 h) component of oxLDL-induced EGFR activation is mediated (at least in part) by 4-HNE (and possibly by other oxidized lipids). This early component is antioxidantinsensitive. 4 The second component (4 ± 5 h) of the oxLDL-induced EGFR activation is antioxidant-sensitive, since it is blocked by antioxidants such as trolox, ca eic acid or PDTC, which act by blocking the cellular oxidative stress (H 2 O 2 generation) evoked by oxLDL. Conversely, exogenous H 2 O 2 induced EGFR autophosphorylation (thus mimicking the second component) and was also inhibited by antioxidants. This e ect is mediated in part through inhibition by oxidative stress of protein tyrosine phosphatases involved in EGFR dephosphorylation.

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“…Plasma LDL is transported across the intact endothelium and becomes trapped in the extracellular matrix of the subendothelial space where it can be subjected to oxidative modifications (9,10). Various cellular and biochemical mediators have been proposed to initiate or regulate LDL oxidation, but which enzymatic or nonenzymatic oxidative mechanisms are implicated in vivo is still the subject of debate and intensive study (11)(12)(13)(14)(15)(16). oxLDL is a potent inducer of inflammatory molecules, but the substances within the oxLDL that are responsible for this effect are only partially known.…”

mentioning

confidence: 99%

Oxidized Low-Density Lipoprotein Promotes Mature Dendritic Cell Transition from Differentiating Monocyte

Perrin-Cocon

Coutant

Agaugué

et al. 2001

The Journal of Immunology

126

115

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Proinflammatory oxidized phospholipids are generated during oxidative modification of low-density lipoproteins (LDL). The production of these proinflammatory oxidized phospholipids is controlled by secreted enzymes that circulate as proteins complexed with LDL and high-density lipoprotein. During the acute phase response to tissue injury, profound changes occur in lipoprotein enzymatic composition that alter their anti-inflammatory function. Monocytes may encounter oxidized phospholipids in vivo during their differentiation to macrophages or dendritic cells (DC). In this study we show that the presence of oxidized LDL (oxLDL) at the first day of monocyte differentiation to DC in vitro yielded phenotypically atypical cells with some functional characteristics of mature DC. Addition of oxLDL during the late stage of monocyte differentiation gave rise directly to phenotypically mature DC with reduced uptake capacity, secreting IL-12 but not IL-10, and supporting both syngeneic and allogeneic T cell stimulation. In contrast to known mediators of DC activation, oxLDL did not trigger maturation of immature DC. An intriguing possibility is that a burst of oxidized phospholipids is an endogenous activation signal for the immune system, which is tightly controlled by lipoproteins during the acute phase response.

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The Oxidation of Lipoproteins by Monocytes-Macrophages

Cited by 160 publications

References 118 publications

Mechanism of the antioxidant to pro-oxidant switch in the behavior of dehydroascorbate during LDL oxidation by copper(II) ions

Mechanism of the antioxidant to pro-oxidant switch in the behavior of dehydroascorbate during LDL oxidation by copper(II) ions

Phenolic antioxidants trolox and caffeic acid modulate the oxidized LDL‐induced EGF‐receptor activation

Oxidized Low-Density Lipoprotein Promotes Mature Dendritic Cell Transition from Differentiating Monocyte

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